API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-κB binding elements: Evidence for a positive feed-back loop pathway resulting in unremitting NF-κB activation

Yoshitaka Hosokawa, Hiroko Suzuki, Masao Nakagawa, Tae H. Lee, Masao Seto

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-κB signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-κB binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-κB p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)- carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-κB activation.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume334
Issue number1
DOIs
Publication statusPublished - 2005 Aug 19

Bibliographical note

Funding Information:
This work was supported in part by a Grant-in-Aid for the 2nd Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare and a Grant-in-Aid for Science in Primary Areas (Cancer Research) from the Ministry of Education, Science, Sports and Culture, Japan.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-κB binding elements: Evidence for a positive feed-back loop pathway resulting in unremitting NF-κB activation'. Together they form a unique fingerprint.

Cite this